Tyrosine hydroxylase is an important regulatory enzyme for the biosynthesis of catecholamines. When a single dose of haloperidol, a dopamine antagonist, is administered to rats, there is a rapid increase in the activity of tyrosine hydroxylase in the striatum. The increase in activity is mediated by an increase in the affinity of the enzyme for its pterin cofactor. We have found that when a striatal extract from haloperiodol treated rats is mixed with a striatal extract from control rats, the tyrosine hydroxylase activity is much more than additive. This suggests that there may be an activator of tyrosine hydroxylase present in extracts from treated rats. We have also studied the effect of chronic haloperidol treatment on rat striatal tyrosine hydroxylase. After seven or more daily injections of haloperidol, an additional dose of the drug causes an immediate increase, followed by a sharp decrease, to a level below that of controls, in striatal tyrosine hydroxylase activity. This may represent a compensatory mechanism by which the enzyme adjusts to tissue levels of dopamine.